In the induction of MHC-restricted immune responses, T cells must interact productively with different cell types and therefore must recognize and may distinguish Ia molecules from different cell types. (1)\We will compare B cell Ia and macrophage Ia molecules to determine: (a) whether the glycosylation difference which we have found in I-A and I-E glycoprotein molecules on B cells and macrophages is relevant to T-cell recognition processes, and (b) whether macrophages bear a special class of Ia molecules recognized by T cells. (2)\We will examine the structure of the carbohydrate from B-cell Ia glycoproteins in detail and will determine how it differs from the carbohydrate in macrophage Ia glycoproteins. (3)\We will examine the Ia molecules in two types of mutant animals, B6.C.H-2bm12 and (B6xCBA/N)F1 males (xid), which are each defective in expression of selected I-A molecule determinants and which have concomitant defects in immune responsiveness. There are indications that defective expression of Ia in these mutants may be at least partially due to alterations in post-translational processing of Ia molecules, either independent of or secondary to changes in structural genes. Comparison of Ia processing in the normal and mutant cells should permit description of these expression defects.